Peptide derivatives as inhibitors of NS2B-NS3 protease from Dengue, West Nile, and Zika flaviviruses.

Peptide derivatives as inhibitors of NS2B-NS3 protease from Dengue, West Nile, and Zika flaviviruses. Bioorg Med Chem. 2019 Jul 23;: Authors: da Silva-Júnior EF, de Araújo-Júnior JX Abstract Currently, more than 70 flaviviruses were identified and reported in the literature, whose Dengue (DENV), Zika (ZIKV), and West Nile (WNV) viruses have been responsible for millions of cases of infections worldwide, mainly in developing countries. These viruses are transmitted by the bite of mosquitoes from genus Aedes, or Culex and, in some cases, Stegomyia. Despite numerous efforts to identify a selective, safe, and effective antiviral agent, there is no currently approved drug for the treatment of flaviviral infections. Then, current pharmacological therapy has the objective to treat the clinical symptoms. Various peptidomimetics and peptide-derivatives have been synthesized and evaluated against several biological targets from flaviviruses with different applications, such as diagnosis, E protein inhibitors, entry inhibitors, virucidal inhibitors, and also viral replication inhibitors. Flaviviral replication depends on the NS3pro that is completely activated when it is complexed to its cofactor, NS2B; forming a viral enzymatic complex. The development of NS2B-NS3pro inhibitors is considered a challenging work due to its active site is shallow and open-pocket. In this work, we report all advances involving peptidomimetics, peptide-derived, ...
Source: Bioorganic and Medicinal Chemistry - Category: Chemistry Authors: Tags: Bioorg Med Chem Source Type: research